1. Field of the Invention
The present invention relates to a device and a method for treating ischemic conditions of major organs in the human body. More particularly, the method and the device of the invention relate to the treatment of the heart disease caused by reduction in myocardial blood flow due to the narrowing of the native coronary blood vessels or occlusion of the bypass grafts.
2. Description of the Related Art
Cardiac failure remains one of the leading causes of death in the United States. At the present time, there are two conventional methods of treatment of the cardiac disease at its advanced stage: 1. Coronary artery bypass graft (CABG) surgery is used to mechanically bypass the area of coronary obstruction, and 2. Various interventional cardiology techniques such as percutaneous transluminal coronary angioplasty (PTCA) or intra-coronary stents designed to open up the narrowing vessels to restore adequate blood flow.
The advantages and high success rate of both techniques are widely known. Many of the patients can benefit significantly from either one of these approaches. However, there is a significant number of patients, between 3 to 6 percent according to some estimates, with so-called "diffused" disease where the obstruction of the vessel tree is not limited to a small well defined area and thus can not be treated with existing techniques. In addition, up to 15 percent of cardiac patients have some degree of "diffused" coronary disease and can be only partially revascularized by conventional means.
Many alternative treatment methods are under development for these patients. Once proven in this patient population group, these methods may be widely used for other cardiac patients as well. For the purposes of this description, the term "biobypass" is used to describe broadly these alternative treatments.
The essence of the approach is to promote the growth of new blood vessels to "biologically bypass" the areas of restriction in the coronary vessel tree. This approach is generally known as angiogenesis. Another possible implementation of biobypass is restoring the contractile function of the myocardium by transplanting healthy myocardial cells, or myocytes, in the areas of the heart damaged by the infarction process. The following is a more detailed description of these biobypass techniques as it relates to the method of the present invention.
Angiogenesis is a process of formation of new blood vessels improving perfusion of a particular organ in the human body. This naturally occurring process is well documented in cancer and tumor research literature. Recently, the great variety of approaches using the principles of angiogenesis for treatment of myocardial ischemia has been under evaluation primarily for patients with diffused coronary artery disease. The aim of all these treatment methods is to promote the growth of new blood vessels to improve myocardial perfusion.
J. Anthony Ware and Michael Simons describe several possible ways to induce angiogenesis in the review article entitled "Angiogenesis in ischemic heart disease", Nature Medicine, Volume 3, Number 2, 1997, pages 158-164. They mention various growth factors that when infused in the coronary arteries, promote the growth of new vessels. Examples of such growth factors discussed in the article include the family of vascular endothelial growth factors (VGEF), also known as vascular permeability factors (VPF), various fibroblast growth factors (FGF), transforming growth factors (TGF), hepatocyte growth factors (HGF), platelet derived growth factors (PDGF), and many others. The authors point out the great variety of such agents and their possible combinations that makes it difficult at the present time to determine the best one for clinical use. Another important factor determining the success of the treatment is the delivery method. Several methods are under investigation at the present time: intravenous infusion, intra-coronary infusion, intra-pericardial infusion and intra-myocardial injection are just some examples of delivery methods under consideration.
Another group of methods use gene therapy. Genes, when injected for example in the myocardium muscle, cause the release of various growth factors that in turn promote the formation of blood vessels. Animal studies using the gene transfer of FGF-5 is described by Frank J. Giordano et al in the article entitled "intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart", Nature Medicine, 1996, Volume 2, Number 5, pages 534-539. Initial clinical results with the injection of the VEGF gene transfer (GTx) is described by Douglas W. Losordo et al in the article entitled "Gene therapy for myocardial angiogenesis. Initial clinical results with direct myocardial injection of phVEGF.sub.165 as sole therapy for myocardial ischemia", Circulation, 1998, Volume 98, pages 2800-2804.
The therapeutic use for angiogenesis of the principles behind vasculogenesis, or the natural growth of blood vessels in the embryo by differentiation of angioblasts into blood islands, which then fuse to form a primitive cardiovascular system, is described by Federico Bussolino et al in the article entitled "Molecular mechanisms of blood vessel formation", TIBS, 1997, Volume 22, pages 251-256 and also by Werner Risau in the article entitled "Mechanisms of angiogenesis", Nature, 1997, Volume 386, pages 671-674.
Various angiogenic growth factor treatment methods and gene transfer methods have been described in US patents. Examples of such patents include the following: U.S. Pat. No. 5,792,453 by Hammond; U.S. Pat. No. 5,491,129 by Shatiel; U.S. Pat. No. 5,470,831 by Whitman; U.S. Pat. No. 5,318,957 by Cid; U.S. Pat. No. 5,244,460 by Unger; U.S. Pat. Nos. 4,778,787 and 4,699,788 by Catsimopoolas.
Angiogenesis may potentially be induced by means other than injection of growth factors. It is suggested in the recent literature that trans-myocardial revascularization (TMR) or catheter-based percutaneous myocardial revascularization (PMR) may prove to be a method of inducing a controlled injury to the myocardial muscle which in turn stimulates blood vessel growth and the opening of collateral vessels to perfuse the injured area of the heart. Such devices and methods are described in several US patents such as U.S. Pat. Nos. 5,840,075 and 5,725,521 by Mueller; U.S. Pat. No. 5,713,894 by Murphy--Chutorian; U.S. Pat. No. 5,672,170 by Cho; and U.S. Pat. No. 4,658,817 by Hardy.
In addition to restoring adequate blood supply, the availability of healthy myocardial cells is an important factor in restoring the contractile function of the heart. Various techniques of myocardial cell proliferation and transplantation have been suggested in the prior art to achieve that purpose. For example, U.S. Pat. Nos. 5,580,779 and 5,543,318 by Smith suggest some ways to induce proliferation of myocytes by exposing them in culture to a platelet freeze/thaw extract or by dissociation through sequential enzymatic digestion and plating on a particular growth medium selective for myocardial cell growth.
All of the above mentioned biobypass techniques as well as other techniques of similar nature have at least two common negative aspects: first, they attempt to provide for new blood vessel growth under the conditions of initially compromised coronary blood flow, and second, they take some several weeks to achieve meaningful results.
The first aspect represents a circular phenomenon: biobypass needs enough blood flow to bring the necessary elements to the treatment site. On the other hand, the blood flow was compromised initially which caused the need for biobypass in the first place. Clearly, reduction of blood flow to almost zero in some cases causes the biobypass as well as all other processes in the heat to slow down or cease completely. It would be therefore highly desirable to be able to break that cycle and create more favorable conditions for the biobypass to occur.
The second aspect is that biobypass usually takes between two and five weeks to be completed, as pointed our for example by Losordo in the above referenced article. Many cardiac patients may not be able to wait that long for the results of biobypass. There is a need therefore for a method of biobypass providing instant relief of symptoms for these patients with advanced stages of heart disease.
A new treatment method is needed therefore to address these common problems associated with biobypass techniques.